Inside the Lab: Slowing Down Estrogen Boosters to Treat Breast Cancer

City of Hope scientists have identified a new potential treatment for breast cancers that exhibit a resistance against a common type of drug used to treat the disease.

They discovered SGK3 — a protein-coding gene — is able to boost activation of estrogen, which can cause cancer reoccurrence. Inhibiting SGK3 can potentially slow down or prevent the resistance, improving the outcome of current treatments.

This is the first study that has suggested SGK3 inhibition as a potential effective treatment of breast cancers with AI-resistance.

What problem were you trying to solve when your team began this study?

Seventy percent of breast cancers are estrogen receptor (ER)-positive. Many such breast cancer patients have cancer recurrence after they take aromatase inhibitors, i.e., the drugs to suppress estrogen production. Our goal was to identify the mechanisms of the resistance and find ways to overcome resistance/recurrence.

What did your study find?

It is known that ER becomes hypersensitive to very low concentrations of estrogen after patients are treated with aromatase inhibitors (AIs). Our study has found that SGK3 plays an important role for the ER hypersensitivity by the mechanisms described in the paper. Briefly, SGK3 makes ER more stable and activated in very low concentrations of estrogen.

Why does that matter?

The study reveals a new mechanism of acquired AI resistance and the finding allows us to develop methods to slow down or prevent the resistance, improving the outcome of such treatment.

What does this mean for breast cancer patients?

New drugs can be developed to prevent or slow down the resistance to AI, or cancer recurrence.

What’s next?

The efforts will be to figure out methods to stop the activation of SGK3. Currently, there is no good inhibitor for SGK3. Efforts in this direction will be needed.

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